近年来，对急性髓系白血病分子发病机制的认识不断进步。尽管有新的治疗选择，急性髓系白血病仍然是老年患者的生存挑战。我们最近发现三磷酸水解酶 SAMHD1 是决定 Ara-C 治疗耐药性的因素之一。在这里，我们设计并测试了新型且更简单的病毒样颗粒，其中包含慢病毒蛋白 Vpx，可有效、短暂地降解 SAMHD1 并提高 Ara-C 治疗的功效。在生产过程中添加微量的慢病毒Rev蛋白增强了病毒样颗粒的产生。此外，我们发现我们的第二代病毒样颗粒可有效靶向并降解具有高水平 SAMHD1 的 AML 细胞系中的 SAMHD1，从而提高 Ara-CTP 水平和对 Ara-C 治疗的反应。原发性 AML 母细胞通常对 VLP 治疗反应较差。总之，我们已经能够生成新颖且更简单的病毒样颗粒，可以有效地将 Vpx 传递到目标细胞。© 2024。作者。

Knowledge of the molecular pathogenesis of acute myeloid leukemia has advanced in recent years. Despite novel treatment options, acute myeloid leukemia remains a survival challenge for elderly patients. We have recently shown that the triphosphohydrolase SAMHD1 is one of the factors determining resistance to Ara-C treatment. Here, we designed and tested novel and simpler virus-like particles incorporating the lentiviral protein Vpx to efficiently and transiently degrade SAMHD1 and increase the efficacy of Ara-C treatment. The addition of minute amounts of lentiviral Rev protein during production enhanced the generation of virus-like particles. In addition, we found that our 2nd generation of virus-like particles efficiently targeted and degraded SAMHD1 in AML cell lines with high levels of SAMHD1, thereby increasing Ara-CTP levels and response to Ara-C treatment. Primary AML blasts were generally less responsive to VLP treatment. In summary, we have been able to generate novel and simpler virus-like particles that can efficiently deliver Vpx to target cells.© 2024. The Author(s).